{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T22:52:57Z","timestamp":1767912777522,"version":"3.49.0"},"reference-count":19,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2019,4,30]],"date-time":"2019-04-30T00:00:00Z","timestamp":1556582400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["reference UID\/IC\/4255\/2019"],"award-info":[{"award-number":["reference UID\/IC\/4255\/2019"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Phenylalanine (Phe) tolerance is highly variable in phenylketonuria (PKU) and rarely described in patients aged \u226512 years. Patients \u226512 years of age with PKU were systematically challenged with additional natural protein (NP) if blood Phe levels remained below 480 \u00b5mol\/L (i.e., upper target blood Phe level for patients aged \u226512 years using Portuguese PKU guidelines). In PKU patients, NP tolerance was calculated at baseline and a median of 6 months after systematic challenge with NP whilst patients were maintaining a blood Phe \u2264480 \u03bcmol\/L. Anthropometry was assessed at both times. Routine blood Phe levels were collected. We studied 40 well-controlled PKU patients (10 hyperphenylalaninemia (HPA), 23 mild and 7 classic PKU), on a low-Phe diet with a mean age of 17 years (12\u201329 years). Median daily NP intake significantly increased between assessments (35 vs. 40 g\/day, p = 0.01). Twenty-six patients (65%) were able to increase their median NP intake by a median 12 g\/day (2\u201342 g)\/day and still maintain blood Phe within target range. Out of the previous 26 patients, 20 (77%) (8 HPA, 11 mild and 1 classical PKU) increased NP from animal sources (e.g., dairy products, fish and meat) and 6 patients (23%) (3 mild and 3 classical PKU) from plant foods (bread, pasta, potatoes). Median protein equivalent intake from Phe-free\/low-Phe protein substitute decreased (0.82 vs. 0.75 g\/kg, p = 0.01), while median blood Phe levels remained unchanged (279 vs. 288 \u03bcmol\/L, p = 0.06). Almost two-thirds of patients with PKU tolerated additional NP when challenged and still maintained blood Phe within the national target range. This suggests that some patients with PKU treated by a low-Phe diet only may over restrict their NP intake. In order to minimise the burden of treatment and optimise NP intake, it is important to challenge with additional NP at periodic intervals.<\/jats:p>","DOI":"10.3390\/nu11050995","type":"journal-article","created":{"date-parts":[[2019,5,2]],"date-time":"2019-05-02T03:15:22Z","timestamp":1556766922000},"page":"995","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Over Restriction of Dietary Protein Allowance: The Importance of Ongoing Reassessment of Natural Protein Tolerance in Phenylketonuria"],"prefix":"10.3390","volume":"11","author":[{"given":"Alex","family":"Pinto","sequence":"first","affiliation":[{"name":"Faculty of Health &amp; Human Sciences, University of Plymouth, Plymouth PL6 8BH, UK"},{"name":"Centro de Gen\u00e9tica M\u00e9dica, Centro Hospitalar Universit\u00e1rio do Porto (CHUP), 4099-028 Porto, Portugal"}]},{"given":"Manuela","family":"Ferreira Almeida","sequence":"additional","affiliation":[{"name":"Centro de Gen\u00e9tica M\u00e9dica, Centro Hospitalar Universit\u00e1rio do Porto (CHUP), 4099-028 Porto, Portugal"},{"name":"Centro de Refer\u00eancia na \u00e1rea de Doen\u00e7as Heredit\u00e1rias do Metabolismo, Centro Hospitalar Universit\u00e1rio do Porto-CHUP, 4099-001 Porto, Portugal"},{"name":"Unit for Multidisciplinary Research in Biomedicine, Abel Salazar Institute of Biomedical Sciences, University of Porto-UMIB\/ICBAS\/UP, 4050-313 Porto, Portugal"}]},{"given":"Anita","family":"MacDonald","sequence":"additional","affiliation":[{"name":"Birmingham Women\u2019s and Children\u2019s Hospital, Birmingham B4 6NH, UK"}]},{"given":"Paula","family":"Cristina Ramos","sequence":"additional","affiliation":[{"name":"Centro de Gen\u00e9tica M\u00e9dica, Centro Hospitalar Universit\u00e1rio do Porto (CHUP), 4099-028 Porto, Portugal"}]},{"given":"Sara","family":"Rocha","sequence":"additional","affiliation":[{"name":"Centro de Refer\u00eancia na \u00e1rea de Doen\u00e7as Heredit\u00e1rias do Metabolismo, Centro Hospitalar Universit\u00e1rio do Porto-CHUP, 4099-001 Porto, Portugal"}]},{"given":"Arlindo","family":"Guimas","sequence":"additional","affiliation":[{"name":"Centro de Refer\u00eancia na \u00e1rea de Doen\u00e7as Heredit\u00e1rias do Metabolismo, Centro Hospitalar Universit\u00e1rio do Porto-CHUP, 4099-001 Porto, Portugal"}]},{"given":"Rosa","family":"Ribeiro","sequence":"additional","affiliation":[{"name":"Centro de Refer\u00eancia na \u00e1rea de Doen\u00e7as Heredit\u00e1rias do Metabolismo, Centro Hospitalar Universit\u00e1rio do Porto-CHUP, 4099-001 Porto, Portugal"}]},{"given":"Esmeralda","family":"Martins","sequence":"additional","affiliation":[{"name":"Centro de Refer\u00eancia na \u00e1rea de Doen\u00e7as Heredit\u00e1rias do Metabolismo, Centro Hospitalar Universit\u00e1rio do Porto-CHUP, 4099-001 Porto, Portugal"},{"name":"Unit for Multidisciplinary Research in Biomedicine, Abel Salazar Institute of Biomedical Sciences, University of Porto-UMIB\/ICBAS\/UP, 4050-313 Porto, Portugal"}]},{"given":"Anabela","family":"Bandeira","sequence":"additional","affiliation":[{"name":"Centro de Refer\u00eancia na \u00e1rea de Doen\u00e7as Heredit\u00e1rias do Metabolismo, Centro Hospitalar Universit\u00e1rio do Porto-CHUP, 4099-001 Porto, Portugal"}]},{"given":"Richard","family":"Jackson","sequence":"additional","affiliation":[{"name":"Cancer Research UK Liverpool Cancer Trials Unit, University of Liverpool, Liverpool L69 3GL, UK"}]},{"given":"Francjan","family":"van Spronsen","sequence":"additional","affiliation":[{"name":"Beatrix Children\u2019s Hospital, University Medical Center Groningen, University of Groningen, 9713 Groningen, The Netherlands"}]},{"given":"Anne","family":"Payne","sequence":"additional","affiliation":[{"name":"Faculty of Health &amp; Human Sciences, University of Plymouth, Plymouth PL6 8BH, UK"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4977-8345","authenticated-orcid":false,"given":"J\u00falio","family":"C\u00e9sar Rocha","sequence":"additional","affiliation":[{"name":"Centro de Gen\u00e9tica M\u00e9dica, Centro Hospitalar Universit\u00e1rio do Porto (CHUP), 4099-028 Porto, Portugal"},{"name":"Centro de Refer\u00eancia na \u00e1rea de Doen\u00e7as Heredit\u00e1rias do Metabolismo, Centro Hospitalar Universit\u00e1rio do Porto-CHUP, 4099-001 Porto, Portugal"},{"name":"Centre for Health Technology and Services Research (CINTESIS), 4200-450 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2019,4,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1016\/S0140-6736(10)60961-0","article-title":"Phenylketonuria","volume":"376","author":"Blau","year":"2010","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"155","DOI":"10.2147\/PHMT.S49329","article-title":"Dietary intervention in the management of phenylketonuria: Current perspectives","volume":"7","author":"Rocha","year":"2016","journal-title":"Pediatric Health Med. 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